Curative treatment of autosomal-recessive hyper-IgE syndrome by hematopoietic cell transplantation

Abstract

Autosomal-recessive hyper-IgE syndrome (AR-HIES) is a combined immunodeficiency recently found to be associated with mutations of DOCK8. Clinically, this disorder is characterized beside recurrent bacterial complications, in particular by an unusual susceptibility to extensive cutaneous viral complications and by a high risk for squamous cell carcinoma. Here, we report on lasting control over the disorder in two patients by hematopoietic cell transplantation (HCT). Both patients were suffering from extensive long-lasting cutaneous viral complications, in particular from disfiguring molluscum contagiosum infections, when treated at the age of 10 and 17 years. Donors were matched unrelated, and conditioning was carried out with a combination of fludarabine, melphalan and BM-targeted radioimmunotherapy. Both patients developed stable, full donor cell chimerism, with the exception of persistent lowIgA serum levels and the exception of normal immune functions. Over the course of several months, cutaneous manifestations of viral disease resolved completely and both patients remain clinically well and free of infectious complications at 4 and 2 years, respectively, after transplantation. This represents the first report indicating HCT to be curative in patients with AR-HIES, which should be considered early before life-threatening complications develop, which include malignancies.

Clinical, immunological and genetic features in Taiwanese patients with the phenotype of hyper-immunoglobulin E recurrent infection syndromes (HIES)

“…In addition, combination of cyclosporin A and monthly IVIG interrupts the vicious cycle of itching and scratching to prevent recurrent cellulitis or/and pyoderma (Wolach et al 1996;Etzioni et al 1997). Very recently, successful hematopoietic stem cell transplantation has rescued two STAT3 defective patients from high-grade non-Hodgkin's lymphoma (Goussetis et al 2010) and two DOCK8 deficient patients from refractory cutaneous infections, especially molluscum contagiosum (Gatz et al 2010). Such successful transplantation guides HIES patients under threat of malignant transformation and refractory virus infection to take relatively wiser options.…”

Ten-Year Follow-Up of a DOCK8-Deficient Child With Features of Systemic Lupus Erythematosus

“…It should be considered as early as possible, given the gradual worsening of the disease. [19][20][21][22] Hematopoietic stem cell transplantation has also shown dramatic positive outcomes in various autoimmune diseases, including SLE. 23 …”

RARE PRIMARY IMMUNODEFICIENCY – HYPER-IgE-SYNDROME: CASE REPORT AND LITERATURE REVIEW

“…В последние годы обнадеживающий результат получен при транспланта-ции стволовых клеток. Эта процедура оказалась эффек-тивной и при аутосомно-доминантной [53] и аутосомно-рецессивной форме гипер-IgE-синдрома [54]. По мнению S. A. Gatz с соавт.…”

“…По мнению S. A. Gatz с соавт. [54], при аутосомно-рецессивном вари-анте заболевания трансплантация костного мозга позво-ляет предотвратить развитие жизнеугрожающих ослож-нений, в том числе злокачественных новообразований.…”